Cerebrospinal fluid cytokines in Lyme neuroborreliosis

Background: Lyme neuroborreliosis (LNB) is one of the manifestations of Lyme disease. Although it is known that immune reaction of LNB patients is dominated by Th1 and Th2 responses and patients have elevated numbers of B cells in their cerebrospinal fluid (CSF), not all the cells involved in inflammation and cytokine secretion have been characterized. The current diagnostics of LNB is based on intrathecal production of antibodies. In recent years, the measurement of chemokine CXCL13 concentration from the CSF has been introduced as a new promising diagnostic tool for LNB to complement the antibody-based diagnostic methods. A few other cytokines have also been analyzed as possible diagnostic markers. However, multiplex analyses simultaneously evaluating the concentrations of a large number of different cytokines in the CSF of LNB patients have been lacking thus far. Extensive cytokine profiling CSF samples of LNB patients would also help in understanding the complex immunopathogenesis of LNB.Methods: CSF samples were analyzed from 43 LNB patients, 19 controls, 18 tick-borne encephalitis patients, and 31 multiple sclerosis patients. In addition, CSF samples from 23 LNB patients obtained after the antibiotic treatment were examined. Altogether, the concentrations of 49 different cytokines were determined from all of the samples. The concentrations of 48 different cytokines were analyzed by magnetic bead suspension array using the Bio-Plex Pro Human Cytokine 21- and 27-plex panels, and the concentration of CXCL13 was analyzed by an ELISA based method.Results: Distinct cytokine profiles which were able to distinguish LNB patients from controls, tick-borne encephalitis patients, multiple sclerosis patients, and LNB patients treated with antibiotics were identified. LNB patients had elevated concentrations of all major T helper cell type cytokines (Th1, Th2, Th9, Th17, and Treg) in their CSF.Conclusions: Despite the great differences in the CSF cytokine profiles of different patient groups, CXCL13 still remained as the best marker for LNB. However, IL-1ra might also be helpful as a marker for the antibiotic treatment response. Concerning the immunopathogenesis, this is the first report suggesting the involvement of Th9 cells in the immune response of LNB

The thickening modern: developing a research agenda beyond intensifying rationalism

We engage in a transdisciplinary trial attempting to understand a societal paradigm slide we call the thickening modern. It is a reaction to the modern way of thinking that attempts to cope with the challenges presented by ‘postmodern’ changes. We deliberate the role of rationalism in two political discussions we see as instances of the thickening modern: decision making in religious communities in a secular society and quality in education. In both cases there is a shift to a postmodern ontological uncertainty yet an attempt to epistemologically cling to modern rationality. We sketch a research agenda that would allow understanding beyond the intensifying rationalism of the modern.acceptedVersionPeer reviewe

Sustainable Land Development In An Urban Context

It can be argued that sustainable urban land development depends on the long-term viability and management success of local economic development. It can be further argued that here, economic sustainability is the key. This would furthermore signify a paradigm change to long-term administrative behavior (via an institutional approach), long-term market behavior (heterodox economics approach), and human behavior in actors’ consumption and location choices (behavioral approach). This article examines two criteria within this discourse: innovativeness and social cohesion. In doing so, it proposes a framework for empirical analysis where it is suggested that western, post-socialist and low developed cases choose different strategies due to their different starting points

Bankart versus Latarjet operation as a revision procedure after a failed arthroscopic Bankart repair

Background: An arthroscopic Bankart operation is the most common operative procedure to treat shoulder instability. In case of recurrence, both Bankart and Latarjet procedures are used as revision procedures. The purpose of this study was to compare the re-recurrence rate of instability and clinical results after arthroscopic revision Bankart and open revision Latarjet procedures following failed primary arthroscopic Bankart operations.Methods: Consecutive patients operatively treated for shoulder instability at Turku University Hospital between 2002 and 2013 were analyzed. Patients who underwent a primary arthroscopic Bankart operation followed by a recurrence of instability and underwent a subsequent arthroscopic Bankart or open Latarjet revision operation with a minimum of 1 year of follow-up were called in for a follow-up evaluation. The re-recurrence of instability, Subjective Shoulder Value, and Western Ontario Shoulder Instability index were assessed.Results: Of 69 patients, 48 (dropout rate, 30%) were available for follow-up. Recurrent instability symptoms occurred in 13 patients (43%) after the revision Bankart procedure and none after the revision Latarjet procedure. A statistically and clinically significant difference in the Western Ontario Shoulder Instability index was found between the patients after the revision Bankart and revision Latarjet operations (68% and 88%, respectively; P = .0166).Conclusions: The redislocation rate after an arthroscopic revision Bankart operation is high. Furthermore, patient-reported outcomes remain poor after a revision Bankart procedure compared with a revision Latarjet operation. We propose that in cases of recurring instability after a failed primary Bankart operation, an open Latarjet revision should be considered.</p

Introduction: Studying Successful Public Policy in the Nordic Countries

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Cross cultural adaptation and psychometric properties of the Finnish version of Western Ontario shoulder instability index (WOSI)

Background: Western Ontario shoulder instability index (WOSI) is a widely used disease-specific self-assessment measurement tool for patients with shoulder instability. The main aim of this study was to translate and cross culturally adapt the WOSI into Finnish language and to test its measurement properties. Methods: WOSI was translated in Finnish and adapted into an electronic user interface. 62 male patients with traumatic anteroinferior shoulder instability, programmed for stabilizing shoulder surgery, answered the questionnaire twice preoperatively (2 and 0 weeks), and twice postoperatively (3 and 12 months). Additional scoring tools, such as satisfaction to treatment outcome, subjective shoulder value (SSV), Oxford shoulder instability index (OSIS) and Constant score (CS), were used as comparators. The reliability, validity and responsiveness of WOSI were investigated through statistical analysis. Results: Preoperative test-retest results were available for 49 patients, and 54 patients were available at final follow up. The mean WOSI was 57.8 (SD 20.3), 70.4 (SD 18.9), and 85.9 (SD 15.5), at baseline, 3, and 12 months, respectively. There was a statistically significant mean improvement of 28.8 (SD 24.5) in WOSI between baseline and 12 months (p < 0.0001). The intraclass correlation coefficient for the preoperative WOSI was excellent 0.91. At 12 months WOSI had an excellent Pearson’s correlation coefficient both with SSV (0.69), OSIS (-0.81), and poor with CS (0.25) scores, confirming our a priori hypothesis. There were no detected floor nor ceiling effects for WOSI pre- or postoperatively. The calculated minimal detectable change was 9.2 and the estimated minimal clinically important difference 13.4 to 18.1. Conclusion: Finnish version of WOSI is a reliable and valid tool for assessing health state and improvement after operative treatment of shoulder instability in young male patients.publishedVersionPeer reviewe

Cross cultural adaptation and psychometric properties of the Finnish version of Western Ontario shoulder instability index (WOSI)

Background: Western Ontario shoulder instability index (WOSI) is a widely used disease-specific self-assessment measurement tool for patients with shoulder instability. The main aim of this study was to translate and cross culturally adapt the WOSI into Finnish language and to test its measurement properties.Methods: WOSI was translated in Finnish and adapted into an electronic user interface. 62 male patients with traumatic anteroinferior shoulder instability, programmed for stabilizing shoulder surgery, answered the questionnaire twice preoperatively (2 and 0 weeks), and twice postoperatively (3 and 12 months). Additional scoring tools, such as satisfaction to treatment outcome, subjective shoulder value (SSV), Oxford shoulder instability index (OSIS) and Constant score (CS), were used as comparators. The reliability, validity and responsiveness of WOSI were investigated through statistical analysis.Results: Preoperative test-retest results were available for 49 patients, and 54 patients were available at final follow up. The mean WOSI was 57.8 (SD 20.3), 70.4 (SD 18.9), and 85.9 (SD 15.5), at baseline, 3, and 12 months, respectively. There was a statistically significant mean improvement of 28.8 (SD 24.5) in WOSI between baseline and 12 months (p Conclusion: Finnish version of WOSI is a reliable and valid tool for assessing health state and improvement after operative treatment of shoulder instability in young male patients.</p

Phosphoproteome and drug-response effects mediated by the three protein phosphatase 2A inhibitor proteins CIP2A, SET, and PME-1

Protein phosphatase 2A (PP2A) critically regulates cell signaling and is a human tumor suppressor. PP2A complexes are modulated by proteins such as cancerous inhibitor of protein phosphatase 2A (CIP2A), protein phosphatase methylesterase 1 (PME-1), and SET nuclear proto-oncogene (SET) that often are deregulated in cancers. However, how they impact cellular phosphorylation and how redundant they are in cellular regulation is poorly understood. Here, we conducted a systematic phosphoproteomics screen for phosphotargets modulated by siRNA-mediated depletion of CIP2A, PME-1, and SET (to reactivate PP2A) or the scaffolding A-subunit of PP2A (PPP2R1A) (to inhibit PP2A) in HeLa cells. We identified PP2A-modulated targets in diverse cellular pathways, including kinase signaling, cytoskeleton, RNA splicing, DNA repair, and nuclear lamina. The results indicate nonredundancy among CIP2A, PME-1, and SET in phosphotarget regulation. Notably, PP2A inhibition or reactivation affected largely distinct phosphopeptides, introducing a concept of nonoverlapping phosphatase inhibition- and activation-responsive sites (PIRS and PARS, respectively). This phenomenon is explained by the PPP2R1A inhibition impacting primarily dephosphorylated threonines, whereas PP2A reactivation results in dephosphorylation of clustered and acidophilic sites. Using comprehensive drug-sensitivity screening in PP2A-modulated cells to evaluate the functional impact of PP2A across diverse cellular pathways targeted by these drugs, we found that consistent with global phosphoproteome effects, PP2A modulations broadly affect responses to more than 200 drugs inhibiting a broad spectrum of cancer-relevant targets. These findings advance our understanding of the phosphoproteins, pharmacological responses, and cellular processes regulated by PP2A modulation and may enable the development of combination therapies